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The Lin28/let-7 pathway regulates the mammalian caudal body axis elongation program

ABSTRACT: The Lin28/let-7 pathway regulates the mammalian caudal body axis elongation program

PROVIDER: PRJNA507791 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8268960.fastq.gz	Fastqsanger.gz
	SRR8268961.fastq.gz	Fastqsanger.gz
	SRR8268962.fastq.gz	Fastqsanger.gz
	SRR8268953.fastq.gz	Fastqsanger.gz
	SRR8268954.fastq.gz	Fastqsanger.gz

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The Lin28/let-7 pathway regulates the mammalian caudal body axis elongation program

Project description:The heterochronic genes Lin28a/b and let-7 are well-established regulators of invertebrate development, however their functions in patterning the mammalian body plan remain unexplored. In this study, we discovered a novel function of Lin28/let-7 in controlling caudal vertebrae number during body axis formation. We found that FoxD1-driven overexpression of Lin28a or LIN28B led to a striking increase in caudal vertebrae number, whereas loss of Lin28a stunted tail formation. Accordingly, perturbation of the let-7 microRNA family led to the opposite phenotypes. We further show that overexpressing Lin28a in embryos resulted in increased tail bud cell proliferation, whereas Lin28a KO decreased cellular proliferation. This was accompanied by a transcriptional shift, including down-regulation of the neural marker Sox2, and resulted in a pro-mesodermal phenotype with decreased proportions of neural tissue relative to mesoderm in Lin28a-overexpressing embryos. Strikingly, Lin28a KO and let-7 over-expression demonstrated opposite effects, suggesting that the Lin28/let-7 pathway acts upstream of the signaling pathways controlling the self-renewal and cell fate commitment of neuro-mesodermal progenitors. We propose that Lin28a/b activity controls the pool of caudal progenitors during tail development, promotes their self-renewal potential, is involved in controlling the balance of neural versus mesodermal cell fate decisions, and that progressive down-regulation of Lin28a allows for species-specific vertebral formula to be achieved. These findings suggest that Lin28/let-7 play a role in the regulation of tail length through heterochrony of the body plan.

2019-05-01 | GSE123193 | GEO

Single cell gene expression analysis of zebrafish body elongation

Project description:Single cell gene expression analysis of zebrafish body elongation

| PRJNA727493 | ENA

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [RNA-seq]

Project description:LIN28 is an RNA binding protein with important roles in early embryo development by interaction with let-7 microRNA precursors or mRNAs in cytoplasm. Here, we showed novel roles of LIN28 within the nucleolus in cultured pluripotent stem cells (PSCs). We found Lin28 deficiency led to activation of the 2-cell (2C)-like transcriptional program and repression of the ES cell program. Mechanistically, LIN28 maintains a peri-nucleolar heterochromatin-residing complex to repress 2C activator Dux via association with NCL and TRIM28. Meanwhile, it promotes liquid-liquid phase separation (LLPS) of nucleolar proteins FBL and NCL to support nucleolar function through its RNA binding domains and intrinsic disordered regions. These findings elucidate novel roles for nucleolar LIN28 in coordinately regulating the ES/2C state homeostasis, and shed light on RNA binding protein-mediated nucleolar phase separation mechanisms in PSCs and early embryo development.

2021-09-15 | GSE164418 | GEO

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [ChIP-seq]

2021-09-15 | GSE164221 | GEO

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [ATAC-seq]

2021-09-15 | GSE164130 | GEO

LIN28 Promotes Nucleolar/Ribosomal Functions to Repress the 2C-like Transcriptional Program in Pluripotent Stem Cells [scRNA-seq]

2021-09-15 | GSE164296 | GEO

Genome-wide analysis of RNAs associated with Lin28

Project description:We used immunoprecipitation to pulldown Lin28 associated RNA targets and used genome-wide high throughput deep sequencing to identified those Lin28-associated RNAs. Keywords: Lin28 IP-RNAseq

2011-01-18 | GSE23109 | GEO

Genome-wide analysis of RNAs associated with Lin28

2011-01-18 | E-GEOD-23109 | biostudies-arrayexpress

LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance (HTS)

Project description:LIN28 is a conserved RNA binding protein implicated in pluripotency, reprogramming and oncogenesis. Previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through cross-linking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28 binding sites in a quarter of human transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation and also direct but differing effects on the protein abundance of splicing regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays demonstrated that exogenous LIN28 expression causes widespread downstream alternative splicing changes. These findings identify important regulatory functions of LIN28 via direct mRNA interactions.

2012-09-10 | GSE39872 | GEO

LIN28 eRIP in Differentiating hESCs

Project description:Excluded-volume-effect-optimized RNA-IP (eRIP) of LIN28-associated mRNAs in H1 hESCs. H1s are induced to differentiate into either trophoblast (TE) or neural (N) lineages, and LIN28 eRIP performed at 0hr (Undifferentiated), 12hr TE, 24hr TE and 24hr N

2014-07-21 | E-MTAB-1652 | biostudies-arrayexpress

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